Manage chronic pain with PEA - NL-100
Chronic pain is more than just a nagging pain that refuses to go away. It is a disabling condition that impacts every aspect of our well-being. In contrast to short-term or acute pain that improves with time, chronic pain persists, creating an inflammatory environment in the body and disrupting sleep, daily routines, job performance, and relationships. Common causes include arthritis, fibromyalgia, nerve damage, injury, and diabetes but sometimes the exact cause of chronic pain is never fully identified, which adds to the frustration and emotional toll. Chronic pain is closely linked to depression, anxiety, and sleep issues, creating a cycle that affects a person’s overall well-being.
Over-the-counter painkillers and prescription medications may offer short-term relief, but they often carry serious risks like addiction, tolerance, and unwanted side effects. As a result, people with chronic pain are turning to non-addictive and safer alternatives for pain relief. One natural compound making waves in the pain management space is PEA. It’s emerging as a powerful alternative for nerve pain and other chronic pain conditions. But how exactly does it work?
What is PEA?
Palmitoylethanolamide (PEA) is a naturally occurring compound (fatty acid amide) produced by the body during an injury or when it is experiencing stress or inflammation. PEA works with the body’s natural systems, especially the endocannabinoid system (ECS), to calm overactive immune responses, reduce inflammation, and decrease pain signaling. It also protects nerve cells from inflammatory damage and overstimulation during pain.
ECS is the body's natural pain and inflammation control system, and plays a critical role in keeping our nervous system healthy, well-functioning and well-regulated. ECS also regulates mood, sleep, memory, appetite and immune system responses. The ECS is made up of cannabinoid receptors, endocannabinoids (for example, anandamide), and enzymes responsible for breaking down endocannabinoids.
PEA anti-inflammatory benefits stem from many direct and indirect mechanisms. Why should you take PEA for chronic pain? Let’s discuss how PEA supports the ECS to reduce pain sensitivity and inflammation.
PEA activates cannabinoid receptors: It boosts the levels of the body’s natural endocannabinoids, especially anandamide, often called the “bliss molecule.” Anandamide binds to and activates cannabinoid receptors to help control pain sensitivity and suppress inflammation. Cannabinoid receptors, when activated, help calm pain signals, reduce inflammation, and restore balance in the body.
PEA prevents the break-down of anandamide: Anandamide, an important messenger molecule of the ECS system, regulates mood, eases anxiety, reduces pain signals, supports deep sleep, regulates immune function and controls inflammation. How PEA fits here is that it blocks the enzymes that are involved in the break-down of anandamide, thus boosting its levels and action. This helps anandamide to stay active in the body for a longer period, extending its benefits.
PEA binds to receptors that lower inflammation: PEA activates certain receptors that block the release of enzymes and cytokines known for triggering inflammation. This process also helps cellular repair and healing.
PEA helps calm glial cells: Glial cells are non-neuronal cells present in the brain and the spinal cord (central nervous system). Their main function is to protect the neurons, but they can produce inflammatory molecules and amplify pain signals when overstimulated during a nerve injury, spinal cord trauma, chronic pain conditions or emotional stress. PEA helps to calm overactive glial cells, and also protects the nerve cells from damage and irritation.
Benefits of PEA for chronic pain
Instead of just masking the pain (like painkillers do), PEA controls the inflammation, reduces the sensitivity to the pain and protects nerve cells from the damage. What is so good about PEA is that it works with the body’s own system that controls pain and inflammation, without causing any side effects or developing risk of addiction or dependency. PEA supplements can make a big difference for people suffering from arthritis, nerve pain, back pain, fibromyalgia, migraines, sciatica and other chronic pain conditions.
References:
- Bortoletto et al. Palmitoylethanolamide supplementation for human health: A state-of-the-art systematic review of Randomized Controlled Trials in patient populations. Brain, Behavior, & Immunity – Health. 2025
- Rao et al. Palmitoylethanolamide (Levagen+) for acute menstrual pain: a randomized, crossover, double-blind, placebo-controlled trial. Women and Health. 2025
- Lang-Illievich et al. Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Nutrients. 2023.
- Amanda Rao et al. Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study. Sleep Science and Practice. 2021.
- Steels et al. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology. 2019